Genetic and Developmental Diseases

Question 1

4 main stages in prenatal development

Answer 1

1. Preimplantation embryonic stage (first cleavage to blastocyst)
2. Germ layer formation (embryonic stage)
3. Early organogenesis (organ primordia formation)
4. Definite organogenesis (anatomical and functional maturation of organs)

Question 2

Organogenesis

Answer 2

The production and development of the organs

Question 3

Gamete

Answer 3

A mature reproductive cell (ovum or sperm) with the haploid chromosome number

Question 4

Zygote

Answer 4

A fertilized ovum

Question 5

What comes from the

1. Ectoderm
2. Mesoderm
3. Endoderm

Answer 5

1. Skin and nervous system
2. Muscle, bone, kidneys, heart, vasculature
3. Cells lining the gut cavity, the airways of the respiratory system and other similar structures

Question 6

Early organogenesis

Answer 6

Marked by organ primordia formation

Question 7

Definite organogenesis

Answer 7

Anatomical and functional maturation of organs
When neural tube defects can occur
Weeks 4-8

Question 8

3 types of exogenous teratogens and some examples

Answer 8

1. Physical (x-rays, corpuscular radiation)
2. Chemical (industrial chemicals, drugs, alcohol)
3. Microbial (viruses, bacteria, parasites)

Question 9

Clinical symptoms of fetal alcohol syndrome

Answer 9

Recessed jaw
Thin upper lip
Palpebral abnormalities
Development of internal organs may be impaired
Mental development is affected
Lower than normal IQ
Psychosocial behaviour may be hindered

Question 10

TORCH syndrome

Answer 10

Toxoplasma
(Others)* - EBV, Listeria, Leptospira
Rubella
Cytomegalovirus
Herpes virus

Question 11

Effects of TORCH syndrome

Answer 11

Brain most often affected: microcephaly, mental retardation, neurological symptoms
Eyes: small, inflammation of inside layers, lens clouding
Heart: developmental defect
Liver/lung: inflammation, reactive enlargement of lymph nodes and spleen
Skin lesions: petechial hemorrhages and vesicles (post herpes)

Question 12

Congenital Rubella Syndrome

Answer 12

Now prevented by materal immunization

Microcephaly, microphthalmia, congenital heart disease

Question 13

What is a chromosome made up of?

Answer 13

1/3 each of DNA, RNA, and protein

Question 14

Aneuploidy

Answer 14

Any chromosome number that is not an exact multiple of the haploid number (23)

Question 15

Hyperdiploidy vs hypodiploidy

Answer 15

Hyper: 2n+
Hypo: 2n-

Question 16

Trisomy 21

Answer 16

3 copies of chromosome 21 from non-disjunction during meiosis 1

Question 17

Clinical features of down’s syndrome

Answer 17

Mental retardation
Unique facial features
Eye abnormalities
Gaping mouth and large tongue
Heart disease
Intestinal defects
Hand abnormalities
Abnormalities of toes

Question 18

Which gene controls male development?

Answer 18

SRY

Question 19

Turner’s syndrome

Answer 19

Partial or complete absence of one X chromosome

Question 20

Turner’s syndrome clinical features

Answer 20

Short stature
Heart shaped face
Webbing of neck
Heart disease
Broad chest
Cubitus valgus
Streak ovaries, hypoplastic uterus, amenorrhea (infertile)

Question 21

Klinefelter Syndrome

Answer 21

Describes a group of chromosomal disorders in which there is at least one extra X chromosome in a male karyotype
47,XXY most common

Question 22

Klinefelter Syndrome Clinical features

Answer 22

Tall, long arms and legs
Lack of beard, body and pubic hair
Gynecomastia (breasts)
Female-like hips
Testicular atrophy, infertility

Question 23

WAGR syndrome

Answer 23

11p12-p14 deletions
Wilms tumor of the kindey, Aniridia (no iris), Genital malformation, mental Retardation
Results in loss of several important genes including WT1 (TSG)

Question 24

Balanced reciprocal translocations

Answer 24

No loss or gain of clinically relevant genetic information
Positon change and no phenotype consequences
Reproductive consequences because offspring can inherit unbalanced form of the translocation

Question 25

Alleles

Answer 25

Genes located on the autosomes are all expressed in duplicate (one on each homologous chromosome)

Question 26

Autosomal Dominant Disorders

Answer 26

Apparent in heterozygotes Affected hetero has 50% chance of passing it on Expressed in every generation Unaffected offspring do not transmit the trait

Question 27

Marfan's Syndrome

Answer 27

Autosomal Dominant Clinically: elongated head, eye abnormalities, aortic aneurysm with dissection and exsanguniation, floppy mitral valve, vertebral deformity, long fingers 1 in 5000 Due to a structural defect in fibrillin CT or tendon gets loose and cannot support body structures

Question 28

Familial Hypercholesterolemia

Answer 28

Autosomal Dominant 1 in 500 Mutation in LDL receptor - so cholesterol is not getting removed from blood properly and you get deposits Get atherosclerosis and coronary artery disease Can be managed with a strict low fat diet and statin

Question 29

Autosomal Recessive Disorders

Answer 29

Gene effect apparent only in homozygotes (one copy from each parent, who are usually asymptomatic carriers) More common than autosomal dominant Incidence of disease is lower because heterozygotes aren't effected

Question 30

Cystic fibrosis

Answer 30

Autosomal recessive (1 in 500, carrier 1 in 25) Mutation in CFTR protein (critical for Cl- across cell membrane) Effects all the glandular secretions of exocrine glands (systemic disease - become more viscous) Problems in pancreas, fetal intestine, and bronchi

Question 31

Definitions 1. Meconium ileus 2. Meconium peritonitis

Answer 31

Because of CF 1. Ileus obstruction due to dehydrated contents of intestine 2. Intestinal rupture and dissipation of intestinal contents throughout the abdominal cavity

Question 32

Phenylketonuria

Answer 32

Autosomal recessive Deficiency in phenylalanine hydroxylase (metabolizes phenylalanine to tyrosine) Results in accumulation of phenylpyruvic acid that can cause neurological defects (slow and progressive but irreversible mental retardation) Treat with a strict diet absent of phenylalanine

Question 33

Tay-Sachs Disease

Answer 33

Autosomal recessive Lysosomal storage disease Defect in the function of hexosaminidase A Results in the accumulation of GM2 gangliosides Cells appear lipid filled, swollen, and vacuolated Effects the brain and eyes, death by 3-5 years old

Question 34

X linked Recessive Disorders

Answer 34

Usually only evident in males | Transmitted from an asymptomatic carrier mother

Question 35

Hemophilia

Answer 35

Type A (factor 8) and B (factor 9) Factor A deficiency more common than B because gene is much larger for A 50% have inherited form, other half is spontaneous Multisystemic effects

Question 36

Fragile X Syndrome

Answer 36

``` Fragility of X chromosome CGG triple nucleotide repeat Mental retardation Most common mental retardation in males 1 in 1250 ```

Question 37

Chorionic villus biopsy

Answer 37

At 10-14 weeks Removal of a small amount of CV tissue which gives rise to placental tissue (98% of the time its reflective of the DNA of the fetus) Has some risk for miscarriage

Question 38

Prematurity vs Immaturity

Answer 38

Pre: birth before 30 weeks, weight less than 2500 g Im: weight less than 1500 g

Question 39

Neonatal Respiratory Distress Syndrome

Answer 39

``` Immature pneumocytes type 2 Surfactant deficiency Atelectasis, alveolar, endothelial injury of lungs Hypoxia-hyaline membrane Cerebral intraventricular hemorrhage ```

Question 40

Sudden Infant Death Syndrome

Answer 40

Sudden unexpected death in infants older than 2 months and less than 9 months Cause not known Maternal risk factors (young, low socioeconomic status, drug users, etc) Infant risk factors (premature, previous GI disease) Most common cause of death in infants beyond immediate neonatal period Autopsy shows lack of oxygen